212 research outputs found
Novel xylan-controlled delivery of therapeutic proteins to inflamed colon by the human anaerobic commensal bacterium
No full textINTRODUCTION: Growth factors such as keratinocyte growth factor-2 (KGF-2) and transforming growth factor-beta (TGF-β) are important immunoregulatory and epithelial growth factors. They are also potential therapeutic proteins for inflammatory bowel disease. However, owing to protein instability in the upper gastrointestinal tract, it is difficult to achieve therapeutic levels of these proteins in the injured colon when given orally. Furthermore, the short half-life necessitates repeated dosage with large amounts of the growth factor, which may have dangerous side effects, hence the importance of temporal and spatial control of growth factor delivery.METHODS: The human commensal gut bacterium, Bacteroides ovatus, was genetically engineered to produce human KGF-2 or TGF-β1 (BO-KGF or BO-TGF) in a regulated manner in response to the dietary polysaccharide, xylan. The successful application of BO-KGF or BO-TGF in the prevention of dextran sodium sulphate induced murine colitis is presented here.RESULTS: This novel drug delivery system had a significant prophylactic effect, limiting the development of intestinal inflammation both clinically and histopathologically. The ability to regulate heterologous protein production by B ovatus using xylan is both unique and an important safety feature of this drug delivery system.CONCLUSIONS: The use of genetically engineered B ovatus for the controlled and localised delivery of epithelial growth promoting and immunomodulatory proteins has potential clinical applications for the treatment of various diseases targeting the colon.</p
Engineering of a human commensal bacterium for the controlled in vivo delivery of immunomodulatory proteins
No full textEThOS - Electronic Theses Online ServiceGBUnited Kingdo
The development and validation of a scoring tool to predict the operative duration of elective laparoscopic cholecystectomy
No full textPopulation-based cohort study of outcomes following cholecystectomy for benign gallbladder diseases
No full textPredicting the difficult laparoscopic cholecystectomy: development and validation of a pre-operative risk score using an objective operative difficulty grading system
No full textHepatic resection for colorectal metastasis: time to challenge the accepted doctrine
No full textThe selection of patients for resection of colorectal liver metastasis (CRLM) is based around a set of established rules and principles, some of which date back to and have changed little since the mid 1980's. In this paper the authors challenge this accepted doctrine and describe the criteria used for selection of patients for surgery in their own centre, criteria which permit the inclusion of many more patients for potentially curative surgery. They go on to describe methods used to increase resectability and discuss their own results achieved for the resection of CRLM.</p
Cost-effectiveness of emergency versus delayed laparoscopic cholecystectomy for acute gallbladder pathology
No full textPreoperative risk factors for conversion from laparoscopic to open cholecystectomy: a validated risk score derived from a prospective U.K. database of 8820 patients
No full text
Utility of polygenic risk scores (PRS) in predicting pancreatic cancer: a systematic review and meta-analysis of common variant and mixed scores with insights into rare variant analysis
No full textIntroduction: pancreatic cancer remains among the top five causes of cancer-related mortality. Only 18% to 20% of patients present with early-stage, potentially curable disease. Patient risk stratification is critical to increasing the number of individuals eligible for surgery. Polygenic risk scores (PRS), combined with clinical risk factors, offer a promising approach to assess lifetime risk of pancreatic cancer. This systematic review synthesizes the results of all published PRS and mixed models for pancreatic cancer. Methods: we systematically searched MEDLINE, Embase, Ovid and Web of Science databases. Odds ratios reported between risk quintiles were transformed to OR per SD increase in risk score. Reported AUCs were synthesized and compared between PRS and mixed models. Results: 27 studies were identified for formal synthesis. PRS yielded an OR of 1.40 (1.28-1.53) for pancreatic cancer, while mixed models incorporating clinical risk factors showed a higher OR of 1.58 (1.34 - 1.88). The AUCs for PRS was 0.61 (0.58-0.65), compared to 0.70 (0.61-0.80) for mixed models. The predictive power of PRS models was positively correlated with the number of SNPs included in studies. Ancestry significantly influenced prediction accuracy, with an OR of 1.42 (1.30-1.56) in Caucasian populations compared to 1.21 (0.77-1.90) in Asian populations. Conclusions: adding clinical risk factors to PRS models significantly increases their predictive capability. Further research is needed to identify a comprehensive set of risk SNPs, enhance accuracy across diverse populations, and incorporate rare genetic variants. These advancements have the potential to significantly boost the predictive accuracy of PRS and mixed models
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